Method for treating cancer

Abstract

The present invention relates to a method for identifying a truncal neo-antigen in a tumour from a subject which comprises the steps of: i) determining mutations present in a sample isolated from the tumour; and ii) identifying a truncal mutation which is a mutation present in essentially all tumour cells; and iii) identifying a truncal neo-antigen, which is an antigen encoded by a sequence which comprises the truncal mutation.

1 - 54 . (canceled) 
     
     
         55 . A method for expanding a T cell population for use in treatment of cancer in a subject, wherein the expanded T cell population targets a neo-antigen, the method comprising steps of:
 a) providing a sample comprising a T cell population which is capable of specifically recognizing said neo-antigen; and   b) co-culturing the T cell population with a composition comprising the neo-antigen, or neo-antigen peptide, and an antigen presenting cell to expand T cells that target the neo-antigen;   wherein the neo-antigen has been identified in a sample of a tumour from said subject as being a clonal neo-antigen.   
     
     
         56 . The method according to  claim 55  wherein said T cells are selectively expanded using a plurality of clonal neo-antigens or clonal neo-antigen peptides that comprise different clonal mutations. 
     
     
         57 . The method according to  claim 56 , wherein said plurality of peptides comprises from 2 to 100 peptides. 
     
     
         58 . The method according to  claim 56 , wherein said expanded T cell population is enriched with T cells which target clonal neo-antigens relative to the starting sample. 
     
     
         59 . The method according to  claim 55 , wherein said antigen presenting cell has been loaded or pulsed with a peptide derived from said clonal neo-antigen. 
     
     
         60 . The method according to  claim 59  wherein said antigen presenting cell is a dendritic cell. 
     
     
         61 . The method according to  claim 55 , wherein the T cell population is cultured with IL-2 or anti-CD3 and/or CD28 antibodies. 
     
     
         62 . The method according to  claim 55 , wherein the T cell population is isolated from a sample of the tumour of the subject to be treated. 
     
     
         63 . The method according to  claim 62 , wherein the T cell population comprises tumour infiltrating lymphocytes (TILs). 
     
     
         64 . The method according to  claim 55 , wherein the expanded population of T cells comprises CD8+ T cells, CD4+ T cells, or CD8+ and CD4 T+ cells. 
     
     
         65 . The method according to  claim 55 , wherein the expanded T cell population comprises at least a first T that cell targets a first clonal neo-antigen generated by a first clonal mutation and a second T cell that targets a second clonal neo-antigen generated by a second clonal mutation. 
     
     
         66 . A method of treating a cancer in a subject, the method comprising:
 administering to the subject a composition that comprises a T cell population selectively expanded to target one or more clonal neo-antigens present in the cancer.   
     
     
         67 . The method according to  claim 66 , wherein the composition comprises a T cell population selectively expanded using a plurality of clonal neo-antigens or clonal neo-antigen peptides that comprise different clonal mutations present in the cancer. 
     
     
         68 . The method according to  claim 66 , wherein composition comprises an expanded population of clonal neo-antigen-reactive T cells that has a higher activity than a population of T cells from the subject which has not been expanded, as measured by the response of the T cell population to re-stimulation with a clonal neo-antigen peptide. 
     
     
         69 . The method according to  claim 68 , wherein the activity is measured by cytokine production. 
     
     
         70 . The method according to  claim 68 , wherein a higher activity comprises a 5-fold or greater increase in activity. 
     
     
         71 . The method according to  claim 66 , further comprising steps, prior to the administering step, of
 providing a sample comprising a T cell population which is capable of specifically recognizing said one or more clonal neo-antigens; and   co-culturing the T cell population with a composition comprising the one or more clonal neo-antigens, or neo-antigen peptide(s), and an antigen presenting cell, to expand T cells that target the one or more clonal neo-antigens.   
     
     
         72 . The method according to  claim 66 , wherein the cancer is non-small-cell lung cancer (NSCLC) or melanoma. 
     
     
         73 . The method according to  claim 66 , further comprising administering a checkpoint inhibitor to the subject.